R&D status November 2015: DNDi Paediatric HIV programme

HIV can be transmitted to children during pregnancy, delivery, and through breastfeeding. An estimated 2.6 million children below the age of 15 were living with HIV in 2014, close to 90% of whom were in sub-Saharan Africa.

Under the 2013 WHO guidelines, infants under the age of three should be treated with an antiretroviral treatment (ART) combination that includes protease inhibitors (PI). The combination of a boosted PI with two nucleoside reverse transcriptase inhibitors (NRTIs) is considered by many experts as the most effective first-line therapy for infants and children. However, this combination therapy is not being widely used. The only available PI for young children, lopinavir/ritonavir (LPV/r) is not adapted to children considering that the oral solution formulation is unpalatable, contains alcohol, requires refrigeration and is logistically difficult to manage.

HIV-infected children co-infected with tuberculosis (TB) face additional difficulties with their treatments as TB therapies interact negatively with the HIV drugs, reducing their levels in blood and so reducing their effectiveness. A stand-alone ritonavir booster formulation is being developed that can be added to any PI-based paediatric ARV regimen, in order to counteract the negative drug interactions between PIs and rifampicin-containing TB treatment.

DNDi’s paediatric HIV programme includes:

Translation

Two projects in the translation phase:

Two 4-in-1 LPV/r-based FDC granules: The development plan in partnership with Cipla and UNITAID, includes putting together the four drugs needed for the treatment of HIV in children into a single unit, also known as a fixed-dose combination (FDC), which is heat-stable, well taste-masked, solid, does not contain alcohol or inappropriate solvents, and most importantly, is easy to dose. In 2015, following preliminary studies, the best formulation candidates in terms of bioavailability and taste-masking have been chosen for testing in healthy human volunteers in Phase I studies.

Superbooster HIV/TB: The study on the pharmacokinetics and safety of superboosting LPV/r with ritonavir for treatment of children in the weight range of 3-15 kg co-infected with HIV and tuberculosis (TB) in South Africa has recruited 96 patients. An interim analysis of data from 80 study participants carried out in May 2015 showed non inferiority of superboosting LPV/r (1:1) over standard regimen LPV/r (4:1). 80% of the children achieved good viral suppression after 6 months of superboosted ART and TB therapy.There were no reported safety issues related to superboosting. The interim results were presented at the 7th International Workshop on Paediatric HIV in July 2015 and report submitted to the WHO Guidelines Technical Review Team.

Development

One project in the development phase:

LPV/r pellets with NRTI FDC: Cipla Ltd., India, has developed LPV/r pellets (mini-‘melt’ tablet formulation), stored in 40/10 mg capsules, which can be opened and administered orally to small children, allowing the drug to be mixed with food and offering the advantage, over the current liquid formulation of these drugs, of: being alcohol-free, not requiring a cold chain, and being easier to dose correctly. This project plans for large-scale implementation studies to provide supportive clinical data on the acceptability, feasibility, efficacy, safety, and pharmacokinetics (PK) of LPV-based therapies in routine treatment settings and to provide early access to better formulations and facilitate registration in the countries concerned. Recruitment of patients started in Kenya, with over 20 patients included to date. Other countries which will start on the study include Uganda, Tanzania, South Africa, Zimbabwe, and many more. Once the 4-in-1 formulations, which are in development, become available, children will be switched to these formulations.

DNDi also continues to partner with UNITAID, CHAI, and the Medicines Patent Pool to bring together key stakeholders in the Paediatric HIV Treatment Initiative (PHTI) to reduce barriers to the development and delivery of WHO recommended antiretroviral formulations for children.

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About DNDi

Drugs for Neglected Diseases initiative (DNDi) is a collaborative, patients’ needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected patients.

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